Abstract
Historically, much controversy has existed regarding the association of inherited thrombophilias with adverse pregnancy outcomes. Current guidelines recommend screening when there is a personal history of venous thromboembolism (VTE) or when there is a strong family history of thromboembolic disease, but our up to 40 % of physicians may screen contrary to current guidelines. This chapter summarizes the existing evidence for each inherited thrombophilia, and reviews current guidelines.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996;174(5):1584–9.
Rai R et al. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;314(7076):253–7.
Rodger MA et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol. 2008;112(2 Pt 1):320–4.
Davenport WB, Kutteh WH. Inherited thrombophilias and adverse pregnancy outcomes: a review of screening patterns and recommendations. Obstet Gynecol Clin N Am. 2014;41:133–44.
Lockwood C, Wendel G. Practice bulletin no. 124: inherited thrombophilias in pregnancy. Obstet Gynecol. 2011;118(3):730–40.
Wichers IM et al. Assessment of coagulation and fibrinolysis in families with unexplained thrombophilia. Thromb Haemost. 2009;101(3):465–70.
Villani M et al. Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias. J Thromb Haemost. 2012;10(2):223–8.
Lussana F et al. Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis. Thromb Res. 2012;129(6):673–80.
Horton AL et al. Family history of venous thromboembolism and identifying factor V Leiden carriers during pregnancy. Obstet Gynecol. 2010;115(3):521–5.
Branch DW. The truth about inherited thrombophilias and pregnancy. Obstet Gynecol. 2010;115(1):2–4.
Bates SM et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edn). Chest. 2008;133(6 Suppl):844S–86.
Dizon-Townson DS et al. Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol. 1997;177(2):402–5.
Rey E et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901–8.
Bradley LA et al. Can factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes? Results from a targeted evidence-based review. Genet Med. 2012;14(1):39–50.
Rodger MA et al. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med. 2010;7(6), e1000292.
Howley HE, Walker M, Rodger MA. A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction. Am J Obstet Gynecol. 2005;192(3):694–708.
Dizon-Townson D et al. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol. 2005;106(3):517–24.
Jaaskelainen E et al. M385T polymorphism in the factor V gene, but not Leiden mutation, is associated with placental abruption in Finnish women. Placenta. 2004;25(8-9):730–4.
Prochazka M et al. Factor V Leiden in pregnancies complicated by placental abruption. BJOG. 2003;110(5):462–6.
Rogers BB et al. Avascular villi, increased syncytial knots, and hypervascular villi are associated with pregnancies complicated by factor V Leiden mutation. Pediatr Dev Pathol. 2010;13(5):341–7.
Silver RM et al. Prothrombin gene G20210A mutation and obstetric complications. Obstet Gynecol. 2010;115(1):14–20.
Infante-Rivard C et al. Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med. 2002;347(1):19–25.
Alfirevic Z, Roberts D, Martlew V. How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol. 2002;101(1):6–14.
Di Nisio M, Middeldorp S, Buller HR. Direct thrombin inhibitors. N Engl J Med. 2005;353(10):1028–40.
Blumenfeld Z, Brenner B. Thrombophilia-associated pregnancy wastage. Fertil Steril. 1999;72(5):765–74.
Preston FE et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996;348(9032):913–6.
Sanson BJ et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein S-deficient women. Thromb Haemost. 1996;75(3):387–8.
Peng F et al. Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations. Int J Mol Med. 2001;8(5):509–11.
Krabbendam I, Dekker GA. Pregnancy outcome in patients with a history of recurrent spontaneous miscarriages and documented thrombophilias. Gynecol Obstet Invest. 2004;57(3):127–31.
den Heijer M et al. Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost. 1998;80(6):874–7.
Eichinger S. Homocysteine, vitamin B6 and the risk of recurrent venous thromboembolism. Pathophysiol Haemost Thromb. 2003;33(5-6):342–4.
den Heijer M et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood. 2007;109(1):139–44.
Bezemer ID et al. No association between the common MTHFR 677C → T polymorphism and venous thrombosis: results from the MEGA study. Arch Intern Med. 2007;167(5):497–501.
Nurk E et al. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. Am J Med. 2004;117(1):26–31.
Molloy AM et al. Folate status and neural tube defects. Biofactors. 1999;10(2-3):291–4.
Ceyhan ST et al. Thrombophilia-associated gene mutations in women with pregnancies complicated by fetal neural tube defects. Int J Gynaecol Obstet. 2008;101(2):188–9.
Akar N et al. Spina bifida and common mutations at the homocysteine metabolism pathway. Clin Genet. 2000;57(3):230–1.
Molloy AM, Weir DG, Scott JM. Homocysteine, folate enzymes and neural tube defects. Haematologica. 1999;84(Suppl EHA-4):53–6.
Coulam CB et al. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol. 2006;55(5):360–8.
Kutteh WH, Triplett DA. Thrombophilias and recurrent pregnancy loss. Semin Reprod Med. 2006;24(1):54–66.
Brenner B et al. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost. 1999;82(1):6–9.
Sarig G et al. Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril. 2002;77(2):342–7.
Kupferminc MJ et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med. 1999;340(1):9–13.
Castoldi E et al. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood. 2000;96(4):1443–8.
Infante-Rivard C et al. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-control study. N Engl J Med. 1991;325(15):1063–6.
Lockshin MD. Pregnancy loss in the antiphospholipid syndrome. Thromb Haemost. 1999;82(2):641–8.
Lockwood C, Wendel G, Silverman N. ACOG Practice Bulletin no. 138. Thromboembolism in Pregnancy. Obstet Gynecol 2013;122(3);706–16.
Lonn E et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567–77.
Kutteh WH. Novel strategies for the management of recurrent pregnancy loss. Semin Reprod Med. 2015;33:159–66.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Kutteh, W.H. (2016). Inherited and Acquired Thrombophilias and Adverse Pregnancy Outcomes. In: Bashiri, A., Harlev, A., Agarwal, A. (eds) Recurrent Pregnancy Loss. Springer, Cham. https://doi.org/10.1007/978-3-319-27452-2_5
Download citation
DOI: https://doi.org/10.1007/978-3-319-27452-2_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27450-8
Online ISBN: 978-3-319-27452-2
eBook Packages: MedicineMedicine (R0)